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Vitamin K Question

In a recent conversation, I was asked about the safety of Vitamin K supplements in relation to cardiovascular health. The gentleman I was speaking with brought up the possibility of excessive blood clotting or coagulation. The basis for his concern is that some “blood thinning” medications, such as coumadin (Warfarin), work by antagonizing Vitamin K. What’s more, physicians often recommend limiting Vitamin K consumption via food and supplementation in patients using Vitamin K antagonists. But, what about the majority of the population that isn’t using coumadin or related drugs?

Far and away, the most common use of Vitamin K drugs and supplements is to support the skeletal system. Specifically, the use of high dose Vitamin K2 (45 mg/daily) is being investigated as a means of preventing fractures and osteoporosis in middle-aged to senior men and women. The results of many of these trials have been extremely compelling. For instance, a paper published in the March 2012 issue of Osteoporosis International concluded that supplementing the diets of postmenopausal women with 1,200 mg calcium, 800 IU of Vitamin D and 45 mg of Vitamin K2 per day would likely reduce “the lifetime probability of at least one fracture by 25%”. The mega dosage used in these studies can only be achieved by taking pharmaceutical preparations, which supply 15 mg of Vitamin K2 (menatetrenone) thrice-daily. The fact that this form of Vitamin K is now being investigated as an adjunct medication for use with other anti-osteoporotic drugs is also noteworthy.

Lower dosage forms of Vitamin K are widely available in health food stores and natural pharmacies. At least three studies from 2012 reveal that supplementing with trace amounts of Vitamin K confers significant bone building benefits. The dosages used in the trials varied from between 100 mcg to 360 mcg daily. Two of the three studies included additional ingredients which were likewise intended to support healthy bone metabolism – calcium, fish oil, magnesium and Vitamin D3. A few other distinctions bear mentioning: 1) in one of the trials, a different form of Vitamin K (phylloquinone or K1) also demonstrated improvements in bone mass indices; 2) the form of Vitamin K2 used in the lower-dose studies is known as menaquinone-7, a derivative of natto, a fermented soy food.

Apart from the coagulation issue, Vitamin K is of interest to the cardiovascular system because it assists the body in retaining calcium in bones and out of arteries. Studies involving hemodialysis patients, a population that frequently presents low Vitamin K status, reveal that Vitamin K2 supplementation (135 to 360 mcg/daily) effectively lowers the levels of inactive matrix Gla protein or MGP – a substance which is linked to calcification of the arterial wall. In addition, Vitamin K2 has been inversely associated with the risk of metabolic syndrome and type 2 diabetes, possibly by improving insulin sensitivity. Both of these prevalent health threats markedly increase the risk of developing cardiovascular disease.

In closing, the issue of Vitamin K and blood clotting must be addressed. Anyone who is currently using anticoagulant therapy should not significantly alter Vitamin K intake without proper medical supervision. That said, it may be beneficial and possible to supplement with small quantities of Vitamin K2 while using these medications. However, proper testing and medication adjustments will likely be required. For those not taking anticoagulants, the use of Vitamin K2 supplements (menaquinone-7) in dosages of up to 360 mcg/day does not appear to affect thrombin generation – a measure of blood clotting activity.

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page. You can find the latest research about this topic there!

Click on the following links to learn more about the studies referenced in today’s column:

12 Comments & Updates to “Vitamin K Question”

Based on this column, several clients have inquired about products that meet the specifications mentioned in the paragraphs above. So, here’s a partial list of candidates I think are worth considering:

Vitamin K, as a cofactor in the gamma carboxylation of certain glutamic acid (Gla) residues, has been related to glucose metabolism and insulin sensitivity. Osteocalcin, also known as bone γ-carboxyglutamic acid, increases β-cell proliferation as well as insulin and adiponectin secretion, which improve glucose tolerance and insulin sensitivity. Thus, the purpose of the present study was to examine the possible role of adiponectin as a mediator of glucose homeostasis following phylloquinone supplementation in premonopause women with prediabetes.

METHODS:

Eighty two women were randomized to consume vitamin k1 supplement (n = 39) or placebo (n = 43) for four weeks. Participants in vitamin K1 treatment group received one pearl softgel capsule containing 1000 micrograms phylloquinone while the placebo group received one placebo capsules daily for four weeks. The Blood samples were collected at baseline and after a four-week intervention to quantify osteocalcin, adiponectin, leptin and relevant variables.

BACKGROUND/OBJECTIVES: A relationship between osteocalcin (OC) levels and factors associated with energy metabolism and insulin resistance has been reported recently. The aim of this study was to investigate whether modulation of ostecalcin isoforms via vitamin K1 supplementation would affect glucose metabolism or insulin sensitivity in prediabetic and premenopause women.

SUBJECTS/METHODS: Eighty-two prediabetic women were randomized to consume vitamin K1 supplement (n=39) or placebo (n=43) for 4 weeks. Participants in the vitamin K1 supplement group received one pearl softgel capsule containing 1000 μm of phylloquinone, and the placebo group received one placebo capsule daily for 4 weeks. Blood samples were collected at baseline and after the 4-week intervention period to quantify carboxylated OC (cOC), undercarboxylated OC (ucOC) and relevant variables.

CONCLUSIONS: The results of this study demonstrated that vitamin K1 supplementation for 4 weeks did not affect insulin resistance in premenopausal and prediabetic women but had beneficial effects on glycemic status and insulin sensitivity.

[Intake of vitamins D and K, and their impact on health in female population].

INTRODUCTION: Vitamins D and K are essential for maintaining bone and its deficiency has been associated with several chronic diseases.

OBJECTIVES: To know the intake of vitamins D and K in female population and analyze their involvement on health.

METHODS: Literature research regarding the topic.

RESULTS: Intake of vitamin D in the Spanish female population from 17 to 60 years is lower than the estimated average requirement in the 95.5% of the studied participants and 30.2% of the Spanish population does not meet the established adequate intake for vitamin K. Several studies have emphasized the importance of maintaining optimal nutrition status of vitamin D for its role in the maintenance of bone, but also for its involvement in body weight control and prevention of diseases (cardiovascular disease, type 2 diabetes, cancer). Vitamin K deficiency is also associated with decreased bone density and increased cardiovascular risk besides exerting a protective effect against type 2 diabetes.

CONCLUSIONS: In female population, the intake of vitamin K, but especially vitamin D, is often lower than recommended. Since a worse nutritional status in these vitamins is associated with damage in bone health, weight control, as well as an increased risk of several diseases, it seems appropriate to monitor and improve their intake.

Not all studies yield positive results. But, they’re still important to know about!

J Am Coll Nutr. 2015 Jul 9:1-7.

Effects of Vitamin K on Matrix Metalloproteinase-3 and Rheumatoid Factor in Women with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by an increase in some autoantibodies and proteolytic enzymes, leading to joint destruction. Although recent investigations have considered vitamin K as an anti-inflammatory nutrient with an important role in bone metabolism, there is currently limited information on its efficacy in RA. We aimed to examine the effects of vitamin K1 (phylloquinone) on the biomarker of joint destruction and autoantibody in patients with RA.

MATERIALS AND METHODS: This was a randomized clinical trial in which 64 women with RA who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Vitamin K1 or placebo was administered to the participants for 8 weeks. Baseline characteristics and anthropometric measures were obtained. Clinical status using disease activity score in 28 joints (DAS-28), serum levels of matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF) were assessed before and after the intervention.

RESULTS: The serum level of MMP-3 compared with the baseline values did not change significantly in the groups. However, the serum concentration of RF decreased significantly in the vitamin K1 group (p = 0.041). Intergroup comparison showed no significant change in RF serum level after adjusting for relevant confounders (p > 0.05).

CONCLUSIONS: Vitamin K1 supplementation at 10 mg/day for 8 weeks did not alter joint destruction and immune status in the patients with RA compared with the controls.

Sugar-sweetened carbonated beverage consumption and coronary artery calcification in asymptomatic men and women.

BACKGROUND: Sugar-sweetened carbonated beverage consumption has been linked to obesity, metabolic syndrome, type 2 diabetes, and clinically manifest coronary heart disease, but its association with subclinical coronary heart disease remains unclear. We investigated the relationship between sugar-sweetened carbonated beverage consumption and coronary artery calcium (CAC) in a large study of asymptomatic men and women.

METHODS: This was a cross-sectional study of 22,210 adult men and women who underwent a comprehensive health screening examination between 2011 and 2013 (median age 40 years). Sugar-sweetened carbonated beverage consumption was assessed using a validated food frequency questionnaire, and CAC was measured by cardiac computed tomography. Multivariable-adjusted CAC score ratios and 95% CIs were estimated from robust Tobit regression models for the natural logarithm (CAC score +1).

RESULTS: The prevalence of detectable CAC (CAC score >0) was 11.7% (n = 2,604). After adjustment for age; sex; center; year of screening examination; education level; physical activity; smoking; alcohol intake; family history of cardiovascular disease; history of hypertension; history of hypercholesterolemia; and intake of total energy, fruits, vegetables, and red and processed meats, only the highest category of sugar-sweetened carbonated beverage consumption was associated with an increased CAC score compared with the lowest consumption category. The multivariable-adjusted CAC ratio comparing participants who consumed ≥5 sugar-sweetened carbonated beverages per week with nondrinkers was 1.70 (95% CI, 1.03-2.81). This association did not differ by clinical subgroup, including participants at low cardiovascular risk.

CONCLUSION: Our findings suggest that high levels of sugar-sweetened carbonated beverage consumption are associated with a higher prevalence and degree of CAC in asymptomatic adults without a history of cardiovascular disease, cancer, or diabetes.

Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama study.

BACKGROUND: Whether soy intake is associated with a decreased risk of cardiovascular disease (CVD) remains unclear. A traditional Japanese soy food, natto, contains a potent fibrinolytic enzyme. However, its relation to CVD has not been studied.

OBJECTIVE: We aimed to examine the association of CVD mortality with the intake of natto, soy protein, and soy isoflavones in a population-based cohort study in Japan.

DESIGN: The study included 13,355 male and 15,724 female Takayama Study participants aged ≥35 y. At recruitment in 1992, each subject was administered a validated semiquantitative food-frequency questionnaire. Deaths from CVD were ascertained over 16 y.

RESULTS: A total of 1678 deaths from CVD including 677 stroke and 308 ischemic heart disease occurred during follow-up. The highest quartile of natto intake compared with the lowest intake was significantly associated with a decreased risk of mortality from total CVD after control for covariates: the HR was 0.75 (95% CI: 0.64, 0.88, P-trend = 0.0004). There were no significant associations between the risk of mortality from total CVD and intakes of total soy protein, total soy isoflavone, and soy protein or soy isoflavone from soy foods other than natto. The highest quartiles of total soy protein and natto intakes were significantly associated with a decreased risk of mortality from total stroke (HR = 0.75, 95% CI: 0.57, 0.99, P-trend = 0.03 and HR = 0.68, 95% CI: 0.52, 0.88, P-trend = 0.0004, respectively). The highest quartile of natto intake was also significantly associated with a decreased risk of mortality from ischemic stroke (HR = 0.67, 95% CI:0.47, 0.95, P-trend = 0.03).

CONCLUSION: Data suggest that natto intake may contribute to the reduction of CVD mortality.

Background • Vitamin K1 and K2 are not typically common in a Western diet because they are found in a variety of fermented foods. Vitamin K2 in particular has been demonstrated to restore mitochondrial function and has a key role in production of mitochondrial adenosine triphosphate. Thus, it is reasonable to speculate that dietary supplementation with vitamin K2 could increase the function of muscle with high mitochondrial content (ie, skeletal and cardiac muscle).

Objective • The purpose of this study was to determine if 8 wk of dietary supplementation with Vitamin K2 could alter cardiovascular responses to a graded cycle ergometer test. Design • The study was a randomized controlled trial.

Setting • The study took place in the Applied Physiology Laboratory of the Department of Biological Sciences at the University of North Texas (Denton, TX, USA).

Participants • Participants were aerobically trained males and female athletes (N = 26). Intervention • Participants were randomly assigned either to a control group that received a rice flour placebo or to an intervention group that received vitamin K2. For weeks 1 to 4, participants received 300 mg/d; for weeks 5 to 8, they received 150 mg/d. Subjects assigned to the control group received similar doses to mirror the intervention group. Subjects consumed the supplements during an 8-wk period while they maintained their typical exercise habits.

Outcome Measures • At baseline and postintervention, participants completed a standard, graded exercise test on an electronically braked cycle ergometer. Before the test, participants were fitted with a mouth piece, and their oxygen consumption, carbon dioxide production, respiratory rate, and respiratory exchange ratio were measured. In addition, participants were fitted with skin-mounted electrodes that measured noninvasive cardiac output, stroke volume, and heart rate. To assess the cumulative exercise change, an area-under-the-curve (AUC) value was calculated separately for each outcome variable at each treatment time point.

Results • Vitamin K2 supplementation was associated with a 12% increase in maximal cardiac output, with P = .031, with a trend toward an increase in heart-rate AUC, with P = .070. No significant changes occurred in stroke volume.

Conclusions • Although vitamin K2 supplementation has previously been reported to improve cardiovascular function in diseased patients, to the research team’s knowledge, the current study is the first to report its potential in active individuals. More research is needed to fully evaluate the potential effects of the observed effects.